This proposal is a sent in response to RFA #HD-01-003 to continue funding of a Pediatric Pharmacology Research Unit at Children's Mercy Hospitals and Clinics (CMH) in Kansas City, Missouri as one of the sites within the NICHD Network of PPRU's. The overall objectives of the Unit are: 1) to continue and expand collaborative participation of the CMH PPRU in the PPRU Network for the primary purpose of producing data that will support labeling of drugs for children through the creation of new information and knowledge;and 2) To conduct basic and translational research in developmental pharmacology that will advance our understanding of the impact of genetic- age- and disease-related differences in drug disposition and action (both beneficial and adverse). Specific Aims include: 1) The collaborative conduct of studies of new and currently marketed drugs with priority given to PPRU Network studies;2) The identification, collation, analysis, and interpretation of data from pediatric clinical trials that are sufficient for expansion of pediatric labeling;3) Use of molecular approaches to define the "link" between childhood development, disease expression, drug biotransformation and drug action;4) Use of bioinformatics, pharmacogenomics, metabolomics to explore and define the basis of developmental regulation of important drug metabolizing enzymes and transporters;5) The provision of a unique teaching environment in which pediatricians, medical sub-specialists, clinical pharmacists, nurses and allied health care professionals can gain expertise in clinical investigation and the discipline of pediatric clinical pharmacology. The capability of the investigators and applicant institution to accomplish these objectives and specific aims is demonstrated by: I) effective programmatic composition and administration;2) expertise and resources within the applicant institution;3) previous and current research accomplishments related to the PPRU Network;4) projected programmatic expansion necessary to meet the anticipated increased demands for pediatric clinical trials over the next five years and also, to enhance the integration of translational science into the drug development process;and 5) presentation of two new research proposals which speak directly to the program objectives and are ideally suited for conduct as part of the PPRU Network.